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三叶苷,一种来自[具体来源未给出]的活性二氢查耳酮,通过丝裂原活化蛋白激酶途径介导的细胞凋亡预防小鼠顺铂诱导的肾毒性。

Trilobatin, an Active Dihydrochalcone from , Prevents Cisplatin-Induced Nephrotoxicity via Mitogen-Activated Protein Kinase Pathway-Mediated Apoptosis in Mice.

作者信息

Duan Yue-Yang, Mi Xiao-Jie, Su Wen-Ya, Tang Shan, Jiang Shuang, Wang Zi, Zhao Li-Chun, Li Wei

机构信息

College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.

National and Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun 130118, China.

出版信息

ACS Omega. 2022 Oct 13;7(42):37401-37409. doi: 10.1021/acsomega.2c04142. eCollection 2022 Oct 25.

DOI:10.1021/acsomega.2c04142
PMID:36312396
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9607670/
Abstract

Although naturally occurring flavonoids have shown beneficial effects on the side effects caused by cisplatin, there are few reports on the protective effect of dihydrochalcone on the cisplatin-induced toxicity. Trilobatin (TLB), as the major sweetener and active ingredient in Rehd, is a dihydrochalcone-like compound that can be present in concentrations of up to 10% or more in tender leaves. Herein, a cisplatin-induced acute kidney injury (AKI) model was established to investigate the protective effect and mechanism of TLB against the cisplatin-induced nephrotoxicity in mice. The results showed that TLB significantly reversed the inhibition of CRE, BUN, and MDA levels compared with the cisplatin group. Furthermore, TLB treatment (50 and 100 mg/kg) for 10 days significantly alleviated cisplatin-induced renal pathological changes. TUNEL staining showed that TLB administration can effectively improve the occurrence of apoptosis of renal tissue cells caused by cisplatin exposure. Importantly, western blot analysis verified that TLB alleviated cisplatin-induced nephrotoxicity by regulating the AKT/MAPK signaling pathway and apoptosis. In summary, our findings showed clearly that TLB has a significant preventive effect on cisplatin-induced AKI.

摘要

尽管天然存在的黄酮类化合物已显示出对顺铂引起的副作用具有有益作用,但关于二氢查耳酮对顺铂诱导的毒性的保护作用的报道却很少。三叶苷(TLB)作为蛇葡萄属植物中的主要甜味剂和活性成分,是一种二氢查耳酮类化合物,在嫩叶中的含量可达10%或更高。在此,建立了顺铂诱导的急性肾损伤(AKI)模型,以研究TLB对小鼠顺铂诱导的肾毒性的保护作用及其机制。结果表明,与顺铂组相比,TLB显著逆转了肌酐(CRE)、尿素氮(BUN)和丙二醛(MDA)水平的抑制。此外,TLB(50和100 mg/kg)处理10天显著减轻了顺铂诱导的肾脏病理变化。TUNEL染色显示,给予TLB可有效改善顺铂暴露引起的肾组织细胞凋亡的发生。重要的是,蛋白质印迹分析证实,TLB通过调节AKT/MAPK信号通路和细胞凋亡减轻了顺铂诱导的肾毒性。总之,我们的研究结果清楚地表明,TLB对顺铂诱导的AKI具有显著的预防作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9866/9607670/2122026f6dba/ao2c04142_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9866/9607670/31debea939fc/ao2c04142_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9866/9607670/00e1799c9626/ao2c04142_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9866/9607670/58717703f00e/ao2c04142_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9866/9607670/623e3b2331e1/ao2c04142_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9866/9607670/2122026f6dba/ao2c04142_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9866/9607670/31debea939fc/ao2c04142_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9866/9607670/00e1799c9626/ao2c04142_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9866/9607670/58717703f00e/ao2c04142_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9866/9607670/623e3b2331e1/ao2c04142_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9866/9607670/2122026f6dba/ao2c04142_0006.jpg

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